We propose to develop a novel disposable semiconductor sensor and system able to directly and rapidly read gigabases of de novo sequence. The system is comprehensive, and includes simplified and robust sample preparation technology, and produces data fully compatible with current standards. A new type of semiconductor sensor - an "Ion Torrent Chip" -has been designed and developed to directly detect polymerization of DNA without the need for ANY intermediate enzymatic reactions, chemiluminescence, fluorescence, optics, optical imaging, or other constraints of having to detect light or use unnatural reagents. The system consisting of disposable "Ion Torrent Chips", an integrated chip reader and fluidics, and can be produced at extremely low costs and generate high quality assembled human genome sequence at less then $1,000. At the heart of the system is a semiconductor sensor, with 10's of millions of separate detectors, each capable of sequencing long stretches of DNA. Along with high-speed signal processing, and base-calling algorithms, the system will be able to establish a new gold standard for low cost, diploid assembled genome sequences. Because the heart of the system is a novel sensor built and assembled using standard semiconductor fabrication methodologies, able to sequence without the need for intermediate enzymes, or the constraints of having to image using light, the cost of genome sequencing will continue to fall with each successive generation of denser chips according to Moore's law. PUBLIC HEALTH RELEVANCE: This proposal aims to develop and allow the deployment of genome sequencing technology with a simplicity and cost point to truly democratize and make routine whole genome sequencing. This technology is expected to have a substantial and direct impact on lowering the cost of healthcare, fully enable consumer genomics and usher in the age of personalized medicine. It will also have a profound impact on our understanding of basic biological processes, with direct impact on the generation of biofuels, and other green technologies.